Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials

摘要

Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (G_m) that reflect regulation of ClC-1 Cl~ and Katp K~+ ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (R_(in)) in between action potential trains. Since the fibre length constant (X) could not be determined, however, the calculation of G_m relied on the assumptions that the specific cytosolic resistivity (R_i) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including R_(in) and X as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and R_i. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in G_m that were eventually followed by a ~ 3-fold, fully reversible increase in G_m after the firing of 1450-1800 action potentials. Using this three-electrode method we further show that the latter rise in G_m was closely associated with excitation failures and loss of action potential signal above -20 mV.